This study is designed to continue our analysis of significant immunoregulatory features in the rat model of experimental allergic encephalomyelitis (EAE). One area of emphasis contained within the proposal concerns the possibility that the development of clinical disease involves an interaction between antigen-specific T-cell factors and mast cells. This interaction is postulated to arm the mast cell due to the cytophilic nature of an antigen- specific T-cell factor. In a manner conceptually similar to IgE mediated responses, subsequent interaction of the armed mast cell with specific antigen leads to a slow degranulation of the mast cell with a resulting release of vasoactive amines (VAA). Release of VAA alters capillary permeability facilitating the cascade of cells which culminate in the characteristic mononuclear cell infiltration. Our initial findings support the mast cell hypothesis and we propose to evaluate the nature of this T-cell factor in the rat EAE model. The demonstration of such a factor in this model of central nervous system autoimmunity would allow greater insight into the inductive events leading to the expression of the delayed-type hypersensitivity response which appears to be responsible for EAE. It is our plan to define the optimal in vitro conditions for the production of the factor, to collect and isolate this factor, and to describe its interaction with mast cells and mast cell-like cell lines. The second area of focus in the study of this disease involves the developing immunoregulation in recipients of antigen-specific lymphocytes. We will concentrate on differentiating the immunoregulatory responses that can be elicited in the recipient. For this work four unique cell populations, all reactive with the encephalitogen of myelin-derived basic protein (BP), will be used. Two of the "populations" are derived from a single BP-specific T- cell clone. The populations apparently differ in their stage of "differentiation" which changes under certain in vitro conditions. The defined differenee between these two populations is the variation in the ability to transfer EAE. The remaining two populations are BP-specific spleen cell populations. One of these two populations is obtained directly from BP-immunized donor animals and does not transfer EAE. The second spleen cell population is derived from the first following in vitro stimulation with BP after which this population can adoptively-transfer EAE. We propose to evaluate the recipient response that develops following adoptive transfer of these populations under conditions which include disease prevention. These studies will provide information generally applicable to both the nature and development of autoimmune diseases.